The role of the protein spectrin in evaluating human erythrocyte surface macromolecule mobility and topography will be investigated. To determine how spectrin regulates the distribution of other membrane proteins, the binding of spectrin to the inside surface of spectrin depleted native membranes and to the surface of protein-lipid recombinants will be examined with the aim of isolating the binding site(s) and evaluating the binding affinities under differing physiochemical conditions. To measure the control spectrin exerts on other membrane components, fluorescence bleaching and free-fracture electron microscopy following fusion will be used to evaluate how the molecular associations of spectrin actually influence macromolecule mobility and topography. It is expected that this detailed examination of the structure and associative properties of the spectrin molecule will provide a firm basis for understanding several pathological syndromes of the red cell which have been traced to perturbations in the organization of its membrane.